Pharmacoepidemiology Unit - ODPRN – Ontario Drug Policy

Comprehensive Research Plan: Inhaled
corticosteroids + long-acting beta agonists
(ICS+LABA) for the treatment of asthma
Pharmacoepidemiology Unit
July 10, 2014
30 Bond Street, Toronto ON, M5B 1W8
www.odprn.ca
[email protected]
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Objectives:
1. To examine national and provincial trends in use of asthma drug
therapies across Canada
2. To examine trends in use of asthma drug therapies for asthma in
Ontario
3. To describe characteristics of asthma patients prescribed ICS/LABA
combination products
4. To investigate course of therapy and adherence with asthma drugs in
Ontario
5. To summarize any observational studies evaluating the comparative
effectiveness of ICS/LABA combination products
Objective 1: National and Provincial Trends in Asthma Therapies
Study Design:
Design: Time series analysis with quarterly time intervals
Study period:
• National and provincial trends (IMS Compuscript): October 2009 to
September 2013
• Ontario trends among publically funded prescriptions (ODB): January
2000 to March 2013
Population: All provinces
Data Sources:
• IMS Compuscript: aggregated data for all prescriptions dispensed at
retail pharmacies across Canada
• Ontario Drug Benefit Database (ODB): individual level data for all
publically funded prescriptions dispensed in Ontario to individuals
aged 12 and older.
Study Population:
Inclusion Criteria:
• All privately and publically-funded prescriptions dispensed in Canada for
treatment of asthma, including:
o ICS/LABA combination products
 Fluticasone+salmeterol (Advair, Advair Diskus)
 Budesonide+formoterol (Symbicort)
 Mometasone+formoterol (Zenhale)
o
Other therapies (inhaled corticosteroids, long-acting beta agonists,
long acting muscarinic antagonist, short-acting beta agonists, short
acting muscarinic antagonist, Leukotriene receptor antagonists)
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Outcome(s) of
Interest:
Measured over entire study period (quarterly):
• Number of prescriptions dispensed
• Total cost of prescriptions
• Number of users (Ontario public drug plan only)
Report:
• Overall rates of use by province
• National rates of use by drug
• Distribution of prescriptions by payer (public, private, cash, NIHB)
• Distribution of prescriptions by age (12-17, 18-64, 65+; Ontario public
drug plan only)
Limitations:
•
The IMS data is only available at the prescription and unit level.
Therefore, national and provincial trends in prescribing cannot
differentiate by indication.
Objective 2: Trends in Use of Asthma Drug Therapies for Asthma in Ontario
Study Design:
Design: Time series analysis with annual time intervals
Study period: April 2000 to March 2013
Data Source:
• Ontario Drug Benefit Database (ODB)
Study Population:
Inclusion Criteria:
• All publically-funded prescriptions for ICS/LABA combination products
dispensed in Ontario
• All publically-funded prescriptions for other drug therapies (inhaled
corticosteroids, long-acting beta agonists, long acting muscarinic
antagonist, short-acting beta agonists, short acting muscarinic antagonist,
Leukotriene receptor antagonists)
•
•
Individuals aged 12+ at time of drug dispensing
Individuals with a diagnosis of asthma using the ICES disease cohort
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Outcome(s) of
Interest:
Measured over entire study period (annually)
• Number and rate of users of ICS/LABA products among asthma
patients
• Number of ICS/LABA prescriptions dispensed to asthma patients
• Drug costs
Stratify all analyses by:
• ICS/LABA combination product (Advair, Symbicort, Zenhale)
• Age (12-17, 18-64, 65+)
Limitations:
•
Asthma diagnosis defined via validated dataset developed at ICES.
Although this dataset has 84% sensitivity and 76% specificity, there
may be some misclassification.
Objective 3: Characteristics of Asthma Patients treated with ICS/LABA Combination
Products in Ontario
Study Design:
Design: Cross-sectional analysis
Study period: April 2012 to March 2013
Data Sources:
• Ontario Drug Benefit Database (ODB)
• Canadian Institute for Health Information-Discharge Abstract Database
(CIHI-DAD)
• National Ambulatory Care Reporting System Database (NACRS)
Study Population:
Inclusion Criteria:
• All publically-funded beneficiaries of Ontario with asthma who are
prescribed an ICS/LABA combination product
• Cohort #1: Individuals aged 12-17 at time of ICS/LABA dispensing
• Cohort #2: Individuals aged 18-65 at time of ICS/LABA dispensing
• Cohort #3: Individuals aged 66+ at time of ICS/LABA dispensing
• Past diagnosis with asthma (prior to cohort entry date)
• Cohort Entry Date: defined as date of first prescription for an ICS/LABA
combination product, following 12th, 18th or 66th birthday, over the study
period.
• Index drug: Defined as the specific ICS/LABA product that was prescribed
on cohort entry date (e.g. Advair, Symbicort or Zenhale)
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Variables of Interest:
Limitations:
For each cohort, measure:
• Number of asthma patients treated
• Number and rate of new ICS/LABA users
o New users aged 66 and older defined as having no past
ICS/LABA use in prior 365 days
o New users <66 years of age defined as having a prescription for
any drug in the past 181-365 days and who didn’t have a
prescription for an ICS/LABA in the past 180 days
• Age at cohort entry date
• Proportion of patients who were male
• Proportion of patients residing in LTC at cohort entry
• Proportion of urban residents at cohort entry
• Socioeconomic status (measured using income quintiles at cohort
entry date)
• Asthma severity
o Defined using the prescribed treatment steps outlined in the
Global Initiative for Asthma (GINA) 2014 report.
• Average cost of ICS/LABA prescriptions per person
• Number of puffs dispensed, per user
• Number of puffers dispensed, per user
• Past asthma maintenance therapy (past 1 year):
o ICS
o LABA
o LAMA
o LTRA
o SABA
o SAMA
o Theophylline
o Oral corticosteroids
• Past hospitalization or ED visit for asthma exacerbations (past 1 year)
Stratify analyses by:
• Type of ICS/LABA combination product
o Advair Diskus, Advair HFA, Symbicort, Zenhale
•
Individuals aged 65 are grouped in with those aged 18-64 because –
although they have universal drug coverage, we have incomplete
medical records for these patients in the prior year (e.g. when aged 64)
since they were not eligible for public drug coverage at this time.
Therefore, it is inappropriate to group these in with those aged 66+.
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Objective 4:
a. Adherence to therapy between those treated with combination ICS/LABA products and those
treated with dual therapy of individual ICS and LABA components
b. Typical course of therapy of asthma drugs in Ontario
Study Design:
Design: Cohort Study
Study period: April 2008 to March 2013
• Accrual period: April 2008 to March 2012
• Maximum follow-up date: March 2013 (1 year minimum follow-up)
Data Sources:
• Ontario Drug Benefit Database (ODB)
• Canadian Institute for Health Information-Discharge Abstract Database
(CIHI-DAD)
• National Ambulatory Care Reporting System Database (NACRS)
Study Population:
Inclusion Criteria:
• All publically-funded beneficiaries of Ontario with asthma who initiate
ICS/LABA therapy. Combination therapy defined in 2 ways:
o Receipt of a combination product (e.g. Advair, Symbicort, Zenhale)
o Dual therapy of individual ICS and LABA components (e.g. receipt
of separate ICS and LABA products for use at the same time).
Include any combination of ICS and LABA products (not just those
available in combination products)
• Cohort #1: Individuals aged 12-17 at time of ICS/LABA dispensing
• Cohort #2: Individuals aged 18-65 at time of ICS/LABA dispensing
• Cohort #3: Individuals aged 66+ at time of ICS/LABA dispensing
• Adults aged 12+ at time of ICS/LABA dispensing
• Restrict to those with asthma diagnosis prior to drug initiation
• New users aged 66 and older, defined as having no past ICS/LABA use in
prior 365 days
• New users <66 years of age, defined as having a prescription for any drug
in the past 181-365 days and who didn’t have a prescription for an
ICS/LABA in the past 180 days
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Outcomes of interest:
Duration of ICS/LABA Therapy:
DEFINITION 1: RELAXED DEFINITION OF ADHERENCE
Define ongoing use of ICS/LABA therapy according to receipt of a subsequent
prescription within 180 days of the prior prescription.
DEFINITION 2: STRICT CLINICAL ADHERENCE
Define ongoing use of ICS/LABA therapy according to receipt of a subsequent
prescription within 1.5x days supply of the prior prescription.
For each definition:
• Discontinuation of combination therapy defined as:
o Discontinuation of combination product (set discontinuation date
as date of last prescription)
o Reducing to single agent therapy from dual therapy (set
discontinuation date as the end of the period of continuous use for
the first drug to be discontinued)
•
Censor on:
o End of study period
o Death
o For analysis stratified by ICS/LABA combination, censor on switch
between products
•
Report the following:
o Total number of new ICS/LABA users
o Number of ICS/LABA users with only 1 prescription before
discontinuing
Among patients with more than 1 prescription dispensed over period of
continuous use Report the following:
o Age
o Gender
o Residence in LTC
o Urban vs rural residents
o Socioeconomic status
o Asthma severity
 Defined using the prescribed treatment steps outlined in
the Global Initiative for Asthma (GINA) 2014 report.
o Cost of therapy
o Median duration of therapy
o Percent adherent after: 1 year, 2 years
o Number who discontinued due to death
•
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Outcomes of interest
(continued):
o
o
o
o
o
Past hospitalization or ED visit for asthma exacerbations (past 1
year)
In the 1 year prior to start of ICS/LABA therapy, report any prior
asthma medications:
 No prior use asthma therapy
 ICS
 LABA
 LAMA
 LTRA
 SABA
 SAMA
 Theophylline
 Oral corticosteroids
Over period of ongoing use:
 Number of different ICS/LABA combinations prescribed
(among those on combination therapy only)
 Concomitant use of other asthma treatment options
• ICS
• LABA
• LAMA
• LTRA
• SABA
• SABA
• Theophylline
• Oral corticosteroids
Kaplan Meier curves constructed and log-rank test used to test for
differences
Cox Proportional Hazards models to calculate unadjusted and
adjusted hazard ratio (with 95% CI)
 Adjust for age, sex, asthma severity
Stratify above analysis by:
• Combination Products vs. Dual Therapy
• Type of ICS/LABA combination initiated (for those on combination therapy
only)
Limitations
•
Individuals aged 65 are grouped in with those aged 18-64 because –
although they have universal drug coverage, we have incomplete
medical records for these patients in the prior year (e.g. when aged 64)
since they were not eligible for public drug coverage at this time.
Therefore, it is inappropriate to group these in with those aged 66+.
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Objective 5: To summarize any observational studies evaluating the comparative effectiveness of
ICS/LABA combination products
Objective:
Review of population-based studies investigating comparative effectiveness
and/or safety of ICS/LABA combination products among patients with asthma
Study Population
Children and adults with asthma
Study Design:
Observational studies
• Comparative effectiveness studies
• Safety studies
Study Inclusion
Criteria
1. English Language
2. Published in last 10 years
Interventions
ICS/LABA combination products
Comparators
ICS/LABA combination products (either as a single product or dual therapy)
Outcomes
Any reported outcomes
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